Trial of the route of early nutritional support in critically ill adults.

BACKGROUND: Uncertainty exists about the most effective route for delivery of early nutritional support in critically ill adults. We hypothesized that delivery through the parenteral route is superior to that through the enteral route. METHODS: We conducted a pragmatic, randomized trial involving adults with an unplanned admission to one of 33 English intensive care units. We randomly assigned patients who could be fed through either the parenteral or the enteral route to a delivery route, with nutritional support initiated within 36 hours after admission and continued for up to 5 days. The primary outcome was all-cause mortality at 30 days. RESULTS: We enrolled 2400 patients; 2388 (99.5%) were included in the analysis (1191 in the parenteral group and 1197 in the enteral group). By 30 days, 393 of 1188 patients (33.1%) in the parenteral group and 409 of 1195 patients (34.2%) in the enteral group had died (relative risk in parenteral group, 0.97; 95% confidence interval, 0.86 to 1.08; P=0.57). There were significant reductions in the parenteral group, as compared with the enteral group, in rates of hypoglycemia (44 patients [3.7%] vs. 74 patients [6.2%]; P=0.006) and vomiting (100 patients [8.4%] vs. 194 patients [16.2%]; P<0.001). There were no significant differences between the parenteral group and the enteral group in the mean number of treated infectious complications (0.22 vs. 0.21; P=0.72), 90-day mortality (442 of 1184 patients [37.3%] vs. 464 of 1188 patients [39.1%], P=0.40), in rates of 14 other secondary outcomes, or in rates of adverse events. Caloric intake was similar in the two groups, with the target intake not achieved in most patients. CONCLUSIONS: We found no significant difference in 30-day mortality associated with the route of delivery of early nutritional support in critically ill adults. (Funded by the United Kingdom National Institute for Health Research; CALORIES Current Controlled Trials number, ISRCTN17386141.).

A multicentre, randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of early nutritional support via the parenteral versus the enteral route in critically ill patients (CALORIES).

BACKGROUND: Malnutrition is a common problem in critically ill patients in UK NHS critical care units. Early nutritional support is therefore recommended to address deficiencies in nutritional state and related disorders in metabolism. However, evidence is conflicting regarding the optimum route (parenteral or enteral) of delivery. OBJECTIVES: To estimate the effect of early nutritional support via the parenteral route compared with the enteral route on mortality at 30 days and on incremental cost-effectiveness at 1 year. Secondary objectives were to compare the route of early nutritional support on duration of organ support; infectious and non-infectious complications; critical care unit and acute hospital length of stay; all-cause mortality at critical care unit and acute hospital discharge, at 90 days and 1 year; survival to 90 days and 1 year; nutritional and health-related quality of life, resource use and costs at 90 days and 1 year; and estimated lifetime incremental cost-effectiveness. DESIGN: A pragmatic, open, multicentre, parallel-group randomised controlled trial with an integrated economic evaluation. SETTING: Adult general critical care units in 33 NHS hospitals in England. PARTICIPANTS: 2400 eligible patients. INTERVENTIONS: Five days of early nutritional support delivered via the parenteral (n = 1200) and enteral (n = 1200) route. MAIN OUTCOME MEASURES: All-cause mortality at 30 days after randomisation and incremental net benefit (INB) (at £20,000 per quality-adjusted life-year) at 1 year. RESULTS: By 30 days, 393 of 1188 (33.1%) patients assigned to receive early nutritional support via the parenteral route and 409 of 1195 (34.2%) assigned to the enteral route had died [p = 0.57; absolute risk reduction 1.15%, 95% confidence interval (CI) -2.65 to 4.94; relative risk 0.97 (0.86 to 1.08)]. At 1 year, INB for the parenteral route compared with the enteral route was negative at -£1320 (95% CI -£3709 to £1069). The probability that early nutritional support via the parenteral route is more cost-effective - given the data - is < 20%. The proportion of patients in the parenteral group who experienced episodes of hypoglycaemia (p = 0.006) and of vomiting (p < 0.001) was significantly lower than in the enteral group. There were no significant differences in the 15 other secondary outcomes and no significant interactions with pre-specified subgroups. LIMITATIONS: Blinding of nutritional support was deemed to be impractical and, although the primary outcome was objective, some secondary outcomes, although defined and objectively assessed, may have been more vulnerable to observer bias. CONCLUSIONS: There was no significant difference in all-cause mortality at 30 days for early nutritional support via the parenteral route compared with the enteral route among adults admitted to critical care units in England. On average, costs were higher for the parenteral route, which, combined with similar survival and quality of life, resulted in negative INBs at 1 year. FUTURE WORK: Nutritional support is a complex combination of timing, dose, duration, delivery and type, all of which may affect outcomes and costs. Conflicting evidence remains regarding optimum provision to critically ill patients. There is a need to utilise rigorous consensus methods to establish future priorities for basic and clinical research in this area. TRIAL REGISTRATION: Current Controlled Trials ISRCTN17386141. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 28. See the NIHR Journals Library website for further project information.

A case of fatal felodipine overdose.

A 54 year gentleman was admitted to hospital within four hours of taking an overdose of modified release felodipine tablets, with a total dose of approximately 250 mg. The initial management comprised fluid resuscitation, calcium chloride and glucagon. He remained hypotensive and was commenced on hyperinsulinaemia-euglycaemic therapy. Hypotension persisted with the development of progressive metabolic acidosis despite increasing inotropic support, haemofiltration and high dose insulin-dextrose infusions. The patient died 60 hours post overdose. The case highlights the profound, refractory circulatory collapse and lethal consequences of significant calcium channel blocker overdose and also reviews potential management strategies to attempt to reverse these changes. Despite the lack of evidence of whole bowel irrigation in overdose per se, its role in the removal of modified release compounds has not been studied. We would strongly urge emergency departments to consider this therapeutic modality, especially in overdoses involving delayed release preparations of calcium channel blockers, which are extremely toxic in overdose and are associated with very high mortality.

Fast-track failure after cardiac surgery: development of a prediction model.

OBJECTIVE: Risk factors for unsuccessful fast-tracking of cardiac surgery patients have not been collectively defined in the literature. The aim of this study was to determine risk factors for fast-track failure and incorporate them into a predictive fast-track failure score. DESIGN: Prospective observational study. SETTING: Cardiothoracic Department of St Mary's Hospital, London. PATIENTS: Data were collected from April 2003 to April 2005 including 1,084 patients undergoing heart surgery who were admitted into the fast-track unit. INTERVENTIONS: Multifactorial logistic regression was used to develop a propensity score for estimating the likelihood of fast-track failure. MEASUREMENTS AND MAIN RESULTS: One hundred and sixty-nine patients failed fast-track management (15.6%). Independent predictors for fast-track failure were impaired left ventricular function with or without recent acute coronary syndrome (odds ratios 2.89 and 1.65 respectively), re-do operation (one, two, or more vs. none, odds ratio 1.75, 7.98), extracardiac arteriopathy (odds ratio 2.63), preoperative intra-aortic balloon pump (odds ratio 3.09), raised serum creatinine in micromol/L (120-150, >150 vs. <120, odds ratio 1.57, 11.24), and nonelective (odds ratio 3.43) and complex surgery (odds ratio 2.70). Model validation showed very good discrimination (area under the curve = 0.815) and calibration (c statistic = 8.527, p = .129). CONCLUSIONS: The fast-track failure score incorporates several preoperative factors and has been successfully internally validated; after undergoing external validation and possible recalibration it may be used as a tool to facilitate planning and flow of cardiac surgery patients, based on the predicted probability of failure. Application of this score may limit fast-track failure rates and help to reduce morbidity and cost.